Morphology Of Organic Crystals Research Articles

Quantifying the effect of solvent on the morphology of organic crystals using a statistical thermodynamics approach

A method for predicting the effect of solvent on the morphology of organic crystals is presented, providing an efficient screening tool for identifying ideal crystallization solvents. The solvent effect is estimated by the computation of chemical potentials and activity coefficients of crystal surfaces using a first principles-based statistical thermodynamics approach. Density functional theory and COSMO-RS are utilized to determine the activity coefficients of the crystal growth faces of a selection of active pharmaceutical ingredients (APIs) in solvents across a broad range of polarities. The ability of COSMO-RS to predict and quantify the effects of solvent on crystal growth and morphology is assessed using hierarchical clustering to classify the solvents according to their overall interaction strength with the crystal faces. The COSMO-RS approach allows for a physical interpretation of the predictions in terms of surface polarity and is confirmed by comparison to published experimental data. Herein a methodology is reported for automated computation of the activity coefficients of all solvent-surface pairs directly from the drug crystal structure. The procedure goes beyond the traditional trial-and-error solvent selection process and has the potential to be used as a rapid computational screening tool in pharmaceutical drug development.

Molecular Modelling of the Morphology of Organic Crystals in the Presence of Impurity Species: Recent Applications to Naphthalene, Phenanthrene, and Caprolactam Crystals

ABSTRACT A molecular modelling capability for predicting the purity and morphology of solids manufactured via crystallisation is important in the realisation of a ‘molecule-up’ or product-centred, approach for the optimisation of chemical processes. Recent work on producing the morphology of molecular solids based upon the molecular and crystal chemistry is presented. The approach is based on the atom-atom method for calculating surface attachment energies, and from these relative crystal growth rates as a function of crystallographic growth direction. The computations have been recently [213-15] developed to be able to treat the effects of impurity species that influence morphology. Molecular modelling procedures include an optimisation of the position and orientation of the adsorbed additive within the host lattice hence, simulating the crystal chemistry of the hetero-species within the host lattice. Case studies include naphthalene and phenanthrene in the presence of biphenyl impurity and caprolactam in the presence of synthesis impurities.

Morphology of organic crystals by energy calculations

Morphology of organic crystals by energy calculations

MORPHOLOGY ENGINEERING OF ORGANIC CRYSTALS WITH THE ASSISTANCE OF “TAILOR-MADE” GROWTH INHIBITORS

Abstract Retardation of growth of organic crystals in the presence of additives in solution has been investigated in terms of their crystal structures and the stereochemistry of the additives. A simple correlation has been established between affected directions of growth and structure of the additive. This mecnanism has been successfully applied for monitoring, in a controlled manner, the morphology of organic crystals; this is illustrated for benzamides and benzoic acids. Furthermore, the absolute configuration of polar crystals and chiral molecules has been directly assigned. This is illustrated for the polar crystal of tr-cinnamoyl alanine, and for the molecule of threonine, through morphological changes this molecule induces in the centrosymmetric crystal of serine.